Upper gastrointestinal (GI) diseases affect millions of people annually, leading to recurrent and discomforting symptoms. Exemplary GI diseases include heartburn, reflux, gastroesophogeal reflux disease (GERD), gastritis, and dyspepsia.
Heartburn, or pyrosis, is a sensation of pain or burning located substernally or high in the epigastrium with radiation into the neck and occasionally to the arms. Heartburn is associated with the regurgitation of acid-peptic gastric juices into the esophagus. Acid reflux can lead to heartburn in milder cases and to gastroesophageal reflux disease in severe cases. Reflux symptoms are often treated as an acid problem, and a typical remedy is an antacid. GERD, also referred to as reflux or reflux esophagitis, is a clinical condition in which the reflux of stomach acid into the esophagus is frequent and severe enough to impact a patient's normal functioning, to cause discomfort or pain, and/or to cause damage to the esophagus. It has been estimated by the U.S. Department of Health and Human Services that about seven million people in the United States suffer from GERD.
Gastritis is pathologically an inflammatory process of the stomach, particularly of the gastric mucosa. It has been known that an acute gastritis is often induced by ingestion of anti-inflammatory agents (aspirin, etc.) or alcohol (ethanol), by emotional stress, or by the back-flow of bile into the stomach. Gastritis may occasionally result from a mistaken ingestion of corrosive acid or alkali.
Various approaches and medicines have been developed to treat upper GI conditions associated with damaged or malfunctioning mucosal tissues in the GI tract. Treatment of upper GI tract conditions has been carried out by the use of alkaline agents and gastric acid suppressors or by limiting consumption of foods to bland diets. One approach to relieve symptoms of reflux or gastritis has been to neutralize gastric acid by using antacids. For example, aluminum and magnesium hydroxide (MAALOX® and MYLANTA®) neutralize gastric acidity, resulting in an increase in stomach pH and duodenal bulb pH. Antacids are fast acting and temporary fixes of short duration. They are known to neutralize acid in the stomach and may also act locally in the distal esophagus. However, antacids do not always prevent heartburn when taken before food or beverages that may provoke symptoms.
Another approach to treat upper GI conditions has been to use H2-receptor antagonists, also known as H2-blockers, to inhibit the action of histamine on the parietal cell, which inhibits acid secretion. Examples of H2-receptor antagonists include cimetidine (TAGAMET®), nizatidine (AXID®), ranitidine hydrochloride (ZANTAC®), lansoprazole (PREVACID®), rabeprazole (ACIPHEX®), and famotidine. U.S. Pat. No. 5,667,794 (to Simon et al.) discloses famotidine, an exemplary H2-receptor antagonist used for the treatment of upper GI conditions. However, for many of these medications, there is a delay between consumption and relief from symptoms. Additionally, treatment can be quite costly to the average patient.
Alternatively, upper GI conditions have been treated with proton-pump inhibitors (“PPIs”) which reduce the amount of gastric acid produced by gastric acid-producing cells. These prescription medications include lansoprazole (PREVACID®), esomeprazole (NEXIUM®), omeprazole (PRILOSEC®), pantoprazole (PROTONIX®), and omeprazole IR (ZEGERID®). However, similar to the H2-blockers, the most popular PPIs require a prescription and demonstrate a delay between consumption and relief from symptoms. Various proton pump inhibitors and treatments of GI disorders are disclosed in U.S. Pat. No. 6,132,770 (to Lundberg); U.S. Pat. No. 6,869,615 (to Chen, et al.); and U.S. Pat. No. 4,786,505 (to Lovgren, et al.).
To solve some of the difficulties associated with current treatments, combination treatments of antacids with H2-receptor antagonists or PPIs have been proposed. However, recent studies have shown that H2-receptor antagonists or and PPIs may cause and increase incidence of hip fractures. (See Yang et al., JAMA. 2006 Dec. 27; 296(24):2947-53). U.S. Pat. No. 5,229,137 (to Wolfe) describes compositions and methods which require the simultaneous administration of an H2-receptor antagonist with an antacid to provide immediate, lasting relief from pain, discomfort and symptoms associated with episodic heartburn. WO 92/00102 describes co-administration of H2-receptor antagonists with antacids for treating gastric disorders such as hyperacidity. WO 93/12779 describes compositions of H2 antagonists with antacids for treating gastric disorders such as hyperacidity. U.S. Pat. No. 5,817,340 describes compositions of famotidine with antacids for treating gastrointestinal distress.
U.S. Pat. No. 4,861,592 describes oral compositions containing cimetidine and aluminum hydroxide-magnesium carbonate co-dried gel for treating duodenal, gastric, recurrent and stomal ulceration, and reflux esophagitis. U.S. Pat. No. 4,824,664 describes effervescent compositions containing cimetidine and sodium bicarbonate for treating duodenal and gastric ulcers. U.S. Pat. Nos. 5,169,640 and 5,188,839 describe compositions containing cimetidine, aluminum hydroxide gel, and magnesium hydroxide, for treating duodenal, gastric, recurrent and stomal ulceration, and reflux esophagitis.
While the methods in art have some effectiveness in relieving the pain and discomfort associated with upper GI symptoms, there exists a need for developing innovative compositions and methods for preventing and treating upper-GI symptoms (related to acid reflux) that can be taken quickly, inexpensively, and with fast resolution of symptoms. The present invention addresses these needs with the novel use of antifungal agents.